Alterations of Fas (Apo-1/CD95) gene in non-small cell lung cancer
Alterations of Fas (Apo-1/CD95) gene in non-small cell lung cancer
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DOI：
10.1038/sj.onc.1202769
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发表时间：
1999-06-24
期刊：
影响因子：
8
通讯作者：
Yoo, NJ
中科院分区：
文献类型：
--
作者：
Lee, SH;Shin, MS;Yoo, NJ
Fas（Apo-1/CD 95）是参与细胞死亡信号传导的细胞表面受体。Fas系统在负性生长调节中的关键作用主要在免疫系统中研究，并且癌症患者中Fas基因的体细胞突变仅在淋巴系恶性肿瘤中描述。然而，许多非淋巴肿瘤细胞已被发现是抵抗Fas介导的凋亡，这表明Fas突变，Fas耐药的可能机制之一，可能参与了非淋巴恶性肿瘤的发病机制，以及。本研究应用聚合酶链反应、单链构象多态性和DNA测序技术，对65例非小细胞肺癌患者的Fns基因进行了全编码区和所有剪接位点的突变检测。总的来说，发现5个肿瘤（7.7%）具有I;as突变，这些突变都是错义突变。所鉴定的五个突变中的四个位于已知参与凋亡信号转导的胞质区域（死亡结构域），一个突变位于跨膜结构域。这是第一份关于非淋巴系统恶性肿瘤中I;ns基因突变的报告，这里提供的数据表明，Fns基因的改变可能导致其凋亡功能的丧失，并有助于某些人肺癌的发病机制。
Fas (Apo-1/CD95) is a cell-surface receptor involved in cell death signaling. The key role of the Fas system in negative growth regulation has been studied mostly within the immune system, and somatic mutations of Fas gene in cancer patients have been described solely in lymphoid-lineage malignancies. However, many nonlymphoid tumor cells have been found to be resistant to Fas-mediated apoptosis, which suggests that Fas mutations, one of the possible mechanisms for Fas-resistance, may be involved in the pathogenesis of non-lymphoid malignancies as well. In this study, we have analysed the entire coding region and all splice sites of the Fns gene for the detection of the gene mutations in 65 human nonsmall cell lung cancers by polymerase chain reaction, single strand conformation polymorphism and DNA sequencing. Overall, five tumors (7.7%) were found to have the I;as mutations, which were all missense mutations. Four of the five mutations identified were located in the cytoplasmic region (death domain) known to be involved in the transduction of an apoptotic signal and one mutation was located in the transmembrane domain. This is the first report on the I;ns gene mutations in non-lymphoid malignancies, and the data presented here suggests that alterations of the Fns gene might lead to the loss of its apoptotic function and contribute to the pathogenesis of some human lung cancers.